Hydrocarbons, C9-C11, n-alkanes, <2% aromatics

Endpoint summary

Description of key information

Oral LD₅₀ (rat) > 5000 mg/Kg bw

Inhalation LC₅₀ (rat) > 5000 mg/m³

Dermal LD₅₀ (rabbit) > 2000 mg/Kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1989/03/01-1989/03/15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to or similar to guideline study OECD 401: GLP .

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

only one dose tested

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River France
- Sex: Males (5); Females (5)
- Weight at study initiation: 102-146 g
- Housing: individual
- Diet (e.g. ad libitum): Biosure LAD 1, ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 50%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

A single dose of P-D 20/26 (5g/kg) was administered by oral gavage.

Doses:

5 g/kg

No. of animals per sex per dose:

Male (5), Female (5)

Control animals:

no

Details on study design:

The acute oral toxicity of P-D 20/26 was investigated in a group of 5 male and 5 female rats. Each animal received a single oral dose of 5 g/kg administered by oral gavage. The condition of all animals was observed over a 14 day period following dosing.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality was observed in any of the animals treated with 5 g/kg P-D 20/26.

Clinical signs:

other: Pilo-erection was observed in all rats within five minutes of dosing and throughout the remainder of Day 1. There were no other clinical signs and recovery, as judged by external appearance and behavior, was complete by Day 2.

Gross pathology:

Terminal autopsy findings were normal.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 for P-D 20/26 following oral gavage was >5 g/kg . Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

The acute toxicity of P-D 20/26 was evaluated in rats via oral gavage at a dose of 5 g/kg bw. Observations were made as to the nature, onset, severity, and duration of toxicological signs once per day for a total of 14 days. All animals survived the entire observational period and displayed a low incidence of clinical symptoms.  The animals displayed little or no abnormalities. The LD50 for P-D 20/26 following oral gavage was >5 g/kg. Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1988/5/10 - 1988/5/24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to OECD test guideline 401. GLP.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG
- Age at study initiation: 9 weeks
- Weight at study initiation: males: 179-197g, females: 162-180g
- Fasting period before study: 12-18h
- Housing: individually
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, batch 95/88 rat maintenance diet, ad libitum
- Water (e.g. ad libitum): community tap water from Itingen, ad libitum
- Acclimation period: at least one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: undiluted, as delivered by sponsor
- Amount of vehicle (if gavage): 5000 mg/kg
- Justification: the oral administration was used, because this is one possible route of human exposure during manufacture, handling and use of the test article

Doses:

5000 mg per kg bodyweight

No. of animals per sex per dose:

5 males and 5 females (one dose)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: observations were made as to the nature, onset, severity, and duration of toxicological signs 4 times during day one, and once per day during day 2-15. Body weights were recorded on the test day prior to dosing and on Day 8 and Day 15, and at death for those which succumbed.
- Necropsy of survivors performed: yes

Statistics:

The LOGIT-model could not be applied to the observed rates of death. The toxicity was estimated without use of a statistical model.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality

Clinical signs:

other: 5000 mg/kg: sedation, dyspnea, hunched posture, ruffled fur All animals had recovered until day 5 of the observation

Gross pathology:

All animals were free of abnormalities at postmortem examination.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 for the test material is >5000 mg/kg. Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

C9 -C11 cyclic aliphatics were administered via oral gavage to 5 male and 5 female rats at a dose of 5000 mg/kg to assess acute oral toxicity.  Animals were observed daily for 15 days post dosing.  At a dose of 5000 mg/kg, signs of toxicity were sedation, dyspnea, hunched posture and ruffled fur. All animals had recovered until day 5 of observation and survived to study termination. All animals were free of abnormalities at postmortem examination.  All surviving animals displayed increases in body weight over their day 0 values.  The acute oral LD50 for C9 -C11 cyclic aliphatics is >5000 mg/kg.  Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Two key read across studies from structural analogues available for assessment.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1999/09/29-1999/10/22

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well-documented study report which meets basic scientific principles: GLP.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

An 8hr exposure for 3 consecutive days, one day post-treatment observation

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: WAG/RijCrlBR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deuschland, Sulzfeld, Germany
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 33-50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Test atmosphere was generated by pumping liquid C9-C11 cyclic aliphatic into stainless steel tubing using peristaltic pumps. The tubing was led through a water bath at 74 deg C and the resulting vapour was transported with an air stream from a compressed air source and added to the main airflow system. The test atmospheres were analysed by two total carbon analysers.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

total carbon analysers

Duration of exposure:

8 h

Concentrations:

0 (air), 1 g/m3 (170ppm), 2.5 g/m3 (430ppm), 5 g/m3 (860ppm)

No. of animals per sex per dose:

8 animals per dose

Control animals:

yes

Details on study design:

Animals were exposed to the test atmosphere in modified H100 inhalation chambers Hazleton System Inc., USA). Each chamber was fitted with a manometer that allowed monitoring the slightly negative pressure inside. Three test groups (with one control) comprising of 8 rats each were exposed to Nappar 10 at different concentrations including: 0 (air), 1 g/m3 (170ppm), 2.5 g/m3 (430ppm), 5 g/m3 (860ppm). Animals were exposed to the test atmosphere 8hours/day for 3 consecutive days. All rats were checked for health and viability at least once daily. Body weight was recorded during randomization on days of testing.

Statistics:

All data were analyzed using the SAS statistical software package (v. 6.12). For each test measure, probability of p<= 0.05 were considered significant.

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 5 000 mg/m³ air (nominal)

Exp. duration:

8 h

Remarks on result:

other: no deaths noted after 3 consecutive days of exposure

Mortality:

All animals survived to the end of the study.

Clinical signs:

other: One animal (2.5 g/m3) and three animals (5.0 g/m3) were noted with bloody exudation around the nose and mouth after the third exposure.

Body weight:

No significant changes were noted after exposure.

Gross pathology:

N/A

Other findings:

N/A

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

C9 -C11 cyclic aliphatics were administered via individual inhalation chambers for eight hours to eight Sprague-Dawley rats at vapor concentration of 0 (air), 1 g/m³ (170ppm), 2.5 g/m3 (430ppm), 5 g/m³ (860ppm) for three consecutive days. There was no mortality noted in any of the animals.  Based on the conditions of this study, the LC50 for acute inhalation exposure to C9 -C11 cyclic aliphatics vapor is greater than the highest obtainable vapor concentration (5 g/m³).  Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report equivalent or similar to OECD guideline 403 : GLP.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Age at study initiation: 9-11 weeks
- Weight at study initiation: 245-325 g
- Housing:individually
- Diet (e.g. ad libitum): ad libitum during non-exposure, food withheld while in chamber
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-76
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Exposure apparatus: 150 liter stainless steel inhalation chamber
- Exposure chamber volume: 150 liter
- Temperature, humidity, pressure in air chamber: 75° F, 48%, slight negative pressure to the room


TEST ATMOSPHERE
- Brief description of analytical method used: calibrated infrared monitor
- Samples taken from breathing zone: no



CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

actual vapor concentration of6100 mg/m3

No. of animals per sex per dose:

10 animals/dose (5 males; 5 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Day 0, 7, and 14
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

>= 6 100 mg/m³ air (analytical)

Exp. duration:

4 h

Mortality:

None

Clinical signs:

other: None

Body weight:

Body weight appeared normal throughout experiment. One female lost 2 grams during the Day 7-14 post-exposure observation period.

Gross pathology:

All animals appeared normal.

Other findings:

N/A

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LC50 for acute inhalation exposure to MRD-94-979 vapor is greater than 6100 mg/m3. Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

MRD-94-979 was administered via individual inhalation chambers for four hours to ten Sprague-Dawley rats (5 males, 5 females) to an average actual vapor concentration of 6100 mg/m³ for four hours to assess acute inhalation toxicity. Animals were observed for fourteen days following exposure.  There were no mortality or gross pathological alterations noted in any of the animals.  Based on the conditions of this study, The LC50 for acute inhalation exposure to MRD-94-979 vapor is greater than 6100 mg/m³.  Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 000 mg/m³ air

Quality of whole database:

Two key and two weight of evidence read across studies from structural analogues available for assessment.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1992/11/10-1992/11/24

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well-documented study report which meets basic scientific principles: GLP

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

; 1987 Guidelines

Deviations:

yes

Remarks:

occlusive dressing used

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products
-Sex: Male (3); Female (3)
- Age at study initiation: 12-13 weeks
- Weight at study initiation: Male: 2.01 to 2.21 kg; Female: 2.17 to 2.48 kg
- Housing: individually housed
- Diet (e.g. ad libitum): AgwayCertified Diet RCA Rabbit, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8-day acclimatization

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-70
- Humidity (%): 40 to 60
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day prior to application the trunk of each animal was clipped free of hair. For each treated animal, 5000 mg/kg of MRD-92-405 was applied to the trunk beneath a gauze patch and secured by an occlusive wrap to prevent evaporation. The whole patch assembly was held in place with tape. The patches were left in position for approximately 24 hours. Residual test material was removed and animals were observed 1, 2.5, and 4 hours after dosing and once per day thereafter for a total of 14 days.

Duration of exposure:

24 hours

Doses:

5000 mg/kg: (3) males; (3) female

No. of animals per sex per dose:

Animals: (3) males; (3) female

Control animals:

no

Details on study design:

SCORING SYSTEM: Draize scale
- Dermal response observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Differences between treated and control group mean values for bodyweight gain were analysed by Student's t-test. Where individual variance ratios were significant (P <0.05 or less), Cochrans approximation was applied (Snedecor and Cochran, Statistical Methods, 6th Ed. Iowa State. 1973). Where zero variance was found in one or more groups, intergroup comparison was performed by the Wilcoxon Rank Sum Test.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

There were no animal deaths prior to study termination.

Clinical signs:

other: Well-defined erythema was noted upon removal of the test patches in all animals exposed to MRD-92-405, with edema noted in two animals. At Day 14, three animals were noted as having very slight erythema and only one animal was noted as having well-defined

Gross pathology:

One animal was free of macroscopic abnormalities. Five animals were observed with desquamation.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 of MRD-92-405 was > 5000 mg/kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

Three male and three female rabbits were exposed to MRD-92-405 for 24h via an occluded patch.  Dermal evaluations occurred at 24 hours post patch removal and once daily until the study termination at day 14. Exposure had no affect on viability; all animals survived the exposure.  The LD50 of MRD-92-405 was > 5000 mg/kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1989/01/27 - 1989/02/10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to or similar to guideline study OECD 402: GLP .

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River France
-Sex: Male (5); Female (5)
- Weight at study initiation: 209 to 254 g
- Housing: individually housed
- Diet (e.g. ad libitum): Labsure LAD 1, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 71%
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day prior to application the trunk of each animal was clipped free of hair. For each treated animal, 2000 mg/kg of P-D 20/26 was applied to the trunk beneath a gauze patch and secured by an occlusive wrap to prevent evaporation. The whole patch assembly was held in place with tape. The patches were left in position for approximately 24 hours. Residual test material was removed and animals were observed soon after dosing and twice per day thereafter for a total of 14 days.

Duration of exposure:

24 hours

Doses:

2000 mg/kg: (5) males; (5) female

No. of animals per sex per dose:

Animals: (5) males; (5) female

Control animals:

no

Details on study design:

SCORING SYSTEM: Draize scale
- Dermal response observations: daily
- Other examinations performed: clinical signs, body weight

Statistics:

Differences between treated and control group mean values for bodyweight gain were analysed by Student's t-test. Where individual variance ratios were significant (P <0.05 or less), Cochran's approximation was applied (Snedecor and Cochran, Statistical Methods, 6th Ed. Iowa State. 1973). Where zero variance was found in one or more groups, intergroup comparison was performed by the Wilcoxon Rank Sum Test.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no animal deaths prior to study termination.

Clinical signs:

other: Well-defined erythema accompanied by slight oedema was observed in all five males and one female after removal of the dressings. A small amount of test substance remained on the skin site in these animals. Slight erythema only was observed in the remainin

Gross pathology:

Terminal autopsy findings were normal.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 of P-D 20/26 was > 2000 mg/kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

Five male and five female rabbits were exposed to P-D 20/26 for 24h via an occluded patch.  Dermal evaluations occurred at 24 hours post patch removal and twice daily until the study termination at day 14. Exposure had no affect on viability; all animals survived the exposure.  The LD50 of P-D 20/26 was > 2000 mg/kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report equivalent or similar to OECD guideline : GLP

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton
- Age at study initiation: 19 weeks
- Weight at study initiation: 3.14-3.51
- Housing: individual
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 50 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-71
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

Details on dermal exposure:

TEST SITE
- Area of exposure: shoulder region to lumbar region
- Type of wrap if used: gauze and plastic sleeve


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing, wiped with gauze
- Time after start of exposure: 24h

Duration of exposure:

The test material was applied to the skin at the appropriate dose, covered with a gauze patch, secured with tape, and covered with a plastic sleeve. After ca. 24h of exposure, the plastic sleeve, tape and gauze patch were removed. The skin was then wiped (but not washed) with gauze and water to remove any remaining test material.

Doses:

The test material was applied to the skin at the appropriate dose, covered with a gauze patch, secured with tape, and covered with a plastic sleeve. After ca. 24h of exposure, the plastic sleeve, tape and gauze patch were removed. The skin was then wiped (but not washed) with gauze and water to remove any remaining test material.

No. of animals per sex per dose:

6 animals/dose (3 males; 3 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:2, 4, 24 hours after dosing and daily for 14 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight

Statistics:

The means and standard deviations of the body weights were calculated.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 3 160 mg/kg bw

Mortality:

none

Clinical signs:

other: There was an overall low incidence of clinical in-life observations noted during the study. Observations included nasal discharge, dry rales, alopecia. Topical exposure elicited very slight to well defined erythema in all animals and very slight edema i

Gross pathology:

N/A

Other findings:

N/A

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 for MRD-83-349 is greater than 3160 mg/kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

The acute dermal toxicity of MRD-83-349 was evaluated in rabbits following topical occlusive exposure.  Test material was applied as a single dose of 3160 mg/kg to the clipped backs of 3 male and 3 female rabbits, covered with a gauze patch, and secured with non-irritating tape and a plastic sleeve.  The test material remained in contact with the skin for 24 hours.  Observations were made as to the nature, onset, severity, and duration of toxicological signs 2, 4, and 24 hours after dosing and once per day thereafter, for a total of 14 days.  Dermal responses were evaluated 24 hours after topical application and on Days 3, 7, 10, and 14 according to the Draize method of scoring.  Application of MRD-83-349 at a dose level of 3160 mg/kg showed no evidence of systemic toxicity under the conditions of this study and all animals survived to study termination.  There were no deaths or treatment-related clinical signs.  Topical exposure elicited very slight to well defined erythema in all animals and very slight edema in four animals.  Desquamation was noted in five animals during the study.  By Day 14, all animals were clear of erythema and edema.  Based on the results of this study, the dermal LD50 for MRD-83-349 is greater than 3160 mg/kg.  Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Three key read across studies from structural analogues available for assessment.

Additional information

There is no data available for Hydrocarbons, C9-C11, n-alkanes, >2% aromatics. However, data is available for structural analogues, Nonane; Hydrocarbons, C9-C11, cyclics, < 2% aromatics; Hydrocarbons, C9-C11, isoalkanes, < 2% aromatics; Hydrocarbons, C9-C11, isoalkanes, cyclics, < 2% aromatics; Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics; and Hydrocarbons, C11-C14, isoalkanes, cyclics, < 2% aromatics and presented in the dossier. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

 

Acute Oral Toxicity

 

Hydrocarbons, C9-C11, cyclics, < 2% aromatics

 

C9-C11 cyclic aliphatics were administered via oral gavage to 5 male and 5 female rats at a dose of 5000 mg/Kg to assess acute oral toxicity (ExxonMobil, 1988). Animals were observed daily for 15 days post dosing. At a dose of 5000 mg/Kg, signs of toxicity were sedation, dyspnea, hunched posture and ruffled fur. All animals had recovered until day 5 of observation and survived to study termination. All animals were free of abnormalities at post-mortem examination. All surviving animals displayed increases in body weight over their day 0 values. The acute oral LD₅₀for C9-C11 cyclic aliphatics is >5000 mg/Kg. Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

 

Hydrocarbons, C11-C14, isoalkanes, cyclics, < 2% aromatics

 

The acute toxicity of Hydrocarbons, C11-C14, isoalkanes, cyclics, < 2% aromatics was evaluated in rats via oral gavage at a dose of 5 g/Kg bw (ExxonMobil, 1989). Observations were made as to the nature, onset, severity, and duration of toxicological signs once per day for a total of 14 days. All animals survived the entire observational period and displayed a low incidence of clinical symptoms. The animals displayed little or no abnormalities. The LD₅₀for Hydrocarbons, C11-C14, isoalkanes, cyclics, < 2% aromatics following oral gavage was >5 g/Kg. Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Acute lnhalation Toxicity

 

Nonane

In a study (Nilsen et al., 1988), ten male Sprague-Dawley rats per concentration were exposed to nonane via inhalation at 2414, 3560, 4438, or 5280 ppm for 8 hours.During inhalation all animals were observed at 15 and 30 min. intervals. For the first 8 hours after exposure all animals were observed at hourly, then at 2 hours intervals during daytime for 14 consecutive days. All animals were subjected to complete necropsy which included examination of the external surface of the body, all orifices, and the cranial, thoracic and abdominal cavities and their contents. In addition to general activity, acute effects as coordination difficulties, tremor, spasms and lethality were monitored. The LC₅₀was determined to be ca. 23.76 mg/L and therefore, under the conditions of this study, the test substance is not classified.

 

In a second study (Carpenter et al., 1978), sixteen male rats were exposed to a single 4 hr concentration of n-nonane. Ten rats were pre-selected for the LC₅₀determination; six rats were sacrificed for histological examination, 3 immediately after exposure, 3 after 2 more days post exposure. LC₅₀rats were observed continuously for the first 5 min of exposure, then at 15 and 30 min, and at 30 min intervals until 1 hr post-exposure, and daily thereafter for 14 days. Gross necropsy was performed on all animals at death or sacrifice. Histopathologic evaluation was made of the respiratory tract and liver from 3 rats/group killed at the completion of exposure and 2 days postexposure. Histopathologic evaluation of the respiratory tract, liver, kidney, brain and bone marrow was made on 3 rats/group sacrificed after the 14 day observation period. Micropathological evaluation of tissues taken at necropsy, 14 days following the single 4-hr inhalation periods, revealed no lesion attributable to vapour inhalation. The LC₅₀was determined to be 17 mg/L in male rats.

 

Hydrocarbons, C9-C11, isoalkanes, <2% aromatics

 

In a key study (ExxonMobil, 2001), the test material (Hydrocarbons, C9-C11, isoalkanes, <2% aromatics) was administered via individual inhalation chambers for eight hours to eight Sprague-Dawley rats at vapor concentration of 0 (air), 1 g/m³(170 ppm), 2.5 g/m³(430 ppm), 5 g/m³(860 ppm) for three consecutive days. There was no mortality noted in any of the animals. Based on the conditions of this study, the LC₅₀for acute inhalation exposure to Hydrocarbons, C9-C11, isoalkanes, <2% aromatics vapor is greater than the highest obtainable vapor concentration (5 g/m³). Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Hydrocarbons, C9-C11, isoalkanes, cyclics, < 2% aromatics

 

Hydrocarbons, C9-C11, isoalkanes, cyclics, < 2% aromatics was administered via individual inhalation chambers for four hours to ten Sprague-Dawley rats (5 males, 5 females) to an average actual vapor concentration of 6100 mg/m³for four hours to assess acute inhalation toxicity (ExxonMobil, 1995). Animals were observed for fourteen days following exposure. There were no mortality or gross pathological alterations noted in any of the animals. Based on the conditions of this study, the LC₅₀for acute inhalation exposure to Hydrocarbons, C9-C11, isoalkanes, cyclics, < 2% aromatics vapor is greater than 6100 mg/m³. Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

 

Acute Dermal Toxicity

 

Hydrocarbons, C9-C11, isoalkanes, cyclics, < 2% aromatics

 

The acute dermal toxicity of Hydrocarbons, C9-C11, isoalkanes, cyclics, < 2% aromatics was evaluated in rabbits following topical occlusive exposure (ExxonMoil, 1984). The test material was applied as a single dose of 3160 mg/Kg to the clipped backs of 3 male and 3 female rabbits, covered with a gauze patch, and secured with non-irritating tape and a plastic sleeve. The test material remained in contact with the skin for 24 hours. Observations were made as to the nature, onset, severity, and duration of toxicological signs 2, 4, and 24 hours after dosing and once per day thereafter, for a total of 14 days. Dermal responses were evaluated 24 hours after topical application and on Days 3, 7, 10, and 14 according to the Draize method of scoring. Application of Hydrocarbons, C9-C11, isoalkanes, cyclics, < 2% aromatics at a dose level of 3160 mg/Kg showed no evidence of systemic toxicity under the conditions of this study and all animals survived to study termination. There were no deaths or treatment-related clinical signs. Topical exposure elicited very slight to well defined erythema in all animals and very slight edema in four animals. Desquamation was noted in five animals during the study. By Day 14, all animals were clear of erythema and edema. Based on the results of this study, the dermal LD₅₀for Hydrocarbons, C9-C11, isoalkanes, cyclics, < 2% aromatics is greater than 3160 mg/Kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics

 

Three male and three female rabbits were exposed to Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics for 24h via an occluded patch (ExxonMobil, 1993). Dermal evaluations occurred at 24 hours post patch removal and once daily until the study termination at day 14. Exposure had no effect on viability; all animals survived the exposure. The LD₅₀of Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics was > 5000 mg/Kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Hydrocarbons, C11-C14, isoalkanes, cyclics, < 2% aromatics

 

Five male and five female rabbits were exposed to Hydrocarbons, C11-C14, isoalkanes, cyclics, < 2% aromatics for 24h via an occluded patch (Cepsa Quimica, 1989). Dermal evaluations occurred at 24 hours post patch removal and twice daily until the study termination at day 14. Exposure had no effect on viability; all animals survived the exposure. The LD₅₀of Hydrocarbons, C11-C14, isoalkanes, cyclics, < 2% aromatics was > 2000 mg/Kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

Justification for classification or non-classification

Based on available read across data, Hydrocarbons, C9-C11, n-alkanes, <2% aromatics is minimally toxic via ingestion where the LD₅₀ is >5000 mg/Kg, via dermal exposure where the LD₅₀ is >2000 mg/Kg, and by inhalation where the LC₅₀ >5000 mg/m³. These findings do not warrant classification under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

Hydrocarbons, C9-C11, n-alkanes, <2% aromatics is classified under EU CLP guidelines as a Category 1 aspiration hazard based on its physical and chemical properties (hydrocarbon fluid, viscosity ≤ 20.5 mm²/s).